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Research: From the Superb to the Questionable

F Edward Yazbak MD

It is safe to say that in the last few years,
researchers who dared question a vaccination policy or only
mention vaccination and autism in the same sentence were certain
to get a public and unrelenting flagellation.

I was therefore overjoyed when the
accomplishment of a distinguished researcher in that venue was
recognized. It was certainly wonderful to hear that the Briloff
Committee at Baruch College very recently awarded The Briloff
Prize for 2012 toDr. Gayle DeLong for her
magnificent exposé titled Conflicts of Interest in
Vaccine Safety Research”. In the citation, the Committee
described Dr. DeLong’s publication as “an excellent
exposition of ethical issues and biases in the examination of
conflicts of interests related to vaccine safety research. The
main thrust of this paper is the questioning of the ethics of
industry sponsorship of vaccine use“

Conflicts of interest (COIs) cloud vaccine safety research. Sponsors
of research have competing interests that may impede the objective
study of vaccine side effects. Vaccine manufacturers, health
officials, and medical journals may have financial and bureaucratic
reasons for not wanting to acknowledge the risks of vaccines.
Conversely, some advocacy groups may have legislative and financial
reasons to sponsor research that finds risks in vaccines. Using the
vaccine-autism debate as an illustration, this article details the
conflicts of interest each of these groups faces, outlines the
current state of vaccine safety research, and suggests remedies to
address COIs. Minimizing COIs in vaccine safety research could
reduce research bias and restore greater trust in the vaccine
program.”

Dr. Delong's previous publication (2011) titled "A positive
association found between autism prevalence and childhood
vaccination uptake across the U.S. population [2] was, I
thought, just as remarkable. Its PubMed abstract was also an
informative and clear summary of the author's extensive research:

“The reason for the rapid rise of
autism in the United States that began in the 1990s is a mystery.
Although individuals probably have a genetic predisposition to
develop autism, researchers suspect that one or more environmental
triggers are also needed. One of those triggers might be the
battery of vaccinations that young children receive. Using
regression analysis and controlling for family income and
ethnicity, the relationship between the proportion of children who
received the recommended vaccines by age 2 years and the
prevalence of autism (AUT) or speech or language impairment (SLI)
in each U.S. state from 2001 and 2007 was determined. A positive
and statistically significant relationship was found: The higher
the proportion of children receiving recommended vaccinations, the
higher was the prevalence of AUT or SLI. A 1% increase in
vaccination was associated with an additional 680 children having
AUT or SLI. Neither parental behavior nor access to care affected
the results, since vaccination proportions were not significantly
related (statistically) to any other disability or to the number
of pediatricians in a U.S. state. The results suggest that
although mercury has been removed from many vaccines, other
culprits may link vaccines to autism. Further study into the
relationship between vaccines and autism is warranted.”

***

“The devil made me do it”

Sure!

Except that the devil in this case is usually rectangular, flat
and green and carries the portrait of a US President. The amount
of money recently going from drug and vaccine companies mostly to
helpful doctors but also to several research institutions can only
be described as obscene.

The just updated site opens with the statement: “ProPublica’s
Dollars for Docs database contains more than $2 billion in
payments to doctors, other medical providers and health care
institutions that have been disclosed by 15 pharmaceutical
companies since 2009.”

The sales of the fifteen disclosing companies reportedly
represented 41% of the US Market in 2011.

On another screen,[4]
one can easily search for the names of the
lucky and fortunate recipients of Big Pharma’s largesse.

On a third screen,[5] the
states are listed in alphabetical order
together with the corresponding number of dollars spent as
payments to physicians and institutions in 2011. The four states
with the largest payments to physicians or grants to institutions
were California: $241,788,042, Florida: $168,661,914, Texas:
$161,199,659 and New York: $142,114,783.

The disclosing drug and vaccine companies are listed on the right
of the screen together with the disbursed amounts and the periods
of time during which those dollars were distributed. The most
generous companies in alphabetical order were Astra Zeneca: 236.1M
from 1/2010 to 9/2012, Eli Lilly: 490.6M from1/2009 to 6/2012,
GSK: 238.6M from 4/2009 to 9/2012, Merck: 224.3M from 7/2009 to
9/2012 and last but not least, Pfizer: 538.2M from 7/2009 to
9/2012.

***

The initial investment

A while ago, a few people in high places at the CDC decided that
Danish Autism Research was amazing because as I was told, Denmark
had “a wonderful recording and tabulating system“, even though
Danish autism figures were relatively small and the population of
Denmark was about equal to that of the State of Maryland.

It is not known exactly when the love fest between the CDC and
the Danes began. What is known from documents obtained through the
Freedom of Information Act is that one afternoon the head of the
Developmental Disabilities Section at CDC was worried about
missing the opportunity to undertake and fund a new Autism and MMR
study in Denmark because of lack of funds. She saved the day and
“the study” by e-mailing the Director of the National Immunization
Program at CDC, who was never short of funds, and asking for $
25,000. The e-mail carried a sense of urgency because
someone called “Poul” was leaving very shortly for Denmark and
could get things rolling. Possibly thinking about his own MMR
vaccination program, the NIP Director promptly obliged.

The DD Director had already secured a commitment for another $
25,000 from a supportive Autism Association.[6]
On its web site,
the association explained that in 2000, it “received a $25,000
donation from Merck“… but “To be clear, our unrestricted donation
of $25,000 from Merck in 2000 was not used to fund the Danish
study – or any other vaccine-related studies.”

The investment seemed to have paid off and the definitively
helpful “Big Danish MMR and Autism Study” by Madsen & Co was
created and published[7]
in the New England Journal of Medicine on
November 7, 2002 with great fanfare.

A CDC epidemiologist who had participated in the study was listed
as a co-author.

The following was disclosed with the article:

Supported by grants from the
Danish National Research Foundation; the National Vaccine Program
Office and National Immunization Program, Centers for Disease
Control and Prevention; and the National Alliance for Autism
Research.

A McGill University Epidemiologist who carefully reviewed the
publication promptly disagreed with the authors’ calculations and
conclusions in a Letter to the Editor of the Journal… that was
never published.

Another world-renowned Canadian Epidemiologist also weighed in
about the quality of the study, the CDC connection and the moral
and ethical implications of the situation. In sworn testimony at
the December 10, 2002 Hearing of the Government Reform Committee,
Professor Walter O. Spitzer M.D., M.P.H., F.R.C.P.C, Emeritus
Professor of Epidemiology at McGill University and Emeritus
Editor, Journal of Clinical Epidemiology stated:

“Only 40 cases (13%)
were reviewed. That is very inadequate especially if done for
validity purposes only. To fail to examine all records among the
787 children in the numerators of the cohort (738 in Table 2),
with a clinical multidisciplinary approach leaves the project
wide open to errors and misclassification.

Professor Spitzer then went on
to criticize in detail other epidemiological findings of the study
before turning to what he perceived were the ethical questions
about potential conflicts of interest:

"The concerns are about
the process of funding, the interaction of sponsors with
protocol formulation and approval, compliance with protocol, the
role of investigators vis-a-vis sponsors in the actual conduct
of research and the input of CDC epidemiologists in the
preparation of the report with its conclusions:

a) Was there a protocol?

b) Who approved it?

c) Were there changes as
the study progressed?

d) Who approved the
changes?

e) Who monitored
work-in-progress?

f) Who approved the final
report?

g) Was there a Scientific
Advisory Board?

h) What exactly was the
role of the CDC and its professionals?"

For "Total Transparency" Dr.
Spitzer advocated:

1. That the main protocol
should be published in advance of the fieldwork, notably including
the analysis plan with attendant definitions declared in advance.

2. A Scientific Advisory
Board be created to monitor all phases especially protocol changes
in progress and proposed publications.

3. A Community Advisory Board to look at conflicts of interest in
finances.

***

Having
many
lingering questions about the study results, I tried to get
the sacred “official autism figures” from Denmark through regular
channels and was unable to. Thankfully, a Danish Mom of a child
with autism came to my assistance and was able to send them to me.

I
thought there were several problems with the design and the
figures and asked a good friend, a wonderful statistician, to
review them with me. We then carefully wrote a response to the
“Big Danish Study”, rebutting it point by point. Our paper was
rejected by the Associate Editor of the NEJM but was ultimately
considered, carefully peer-reviewed and published in October
2004.[8]

***

The gift that keeps on giving

As months went on, it became apparent that the CDC’s 25,000
dollars were only a down payment.

Several other “Danish” studies somehow helped by the CDC and in
return, invariably supportive were created and published with
great pride and jubilation. I reviewed most of them in June 2005
in “The CDC finances, writes and helps publish Danish
Research”[9]

Like many, I had no idea how much the Danish Love Affair had cost
the US taxpayers until Wednesday April 13, 2011 when I saw a press
release[10]
from the office of “The United States Attorney’s
Office, Northern District of Georgia” titled:

AUTISM RESEARCHER INDICTED FOR STEALING GRANT
MONEY

“Thorsen Allegedly Absconded With Over $1
Million”

After mentioning that Dr. Poul Thorsen had “been indicted by a
federal grand jury on charges of wire fraud and money laundering
based on a scheme to steal grant money the CDC had awarded to
governmental agencies in Denmark for autism research” the
press release went on to quote three US officials involved with the
case:

“United States Attorney Sally Quillian Yates said of the
case, “Grant money for disease research is a precious
commodity. When grant funds are stolen, we lose not only the
money, but also the opportunity to better understand and cure
debilitating diseases. This defendant is alleged to have
orchestrated a scheme to steal over $1 million in CDC grant money
earmarked for autism research. We will now seek the
defendant’s extradition for him to face federal charges in the
United States.”

“Stealing research grant money to line his pockets, as
Poul Thorsen stands accused of here today, cheats U.S. taxpayers
and will simply not be tolerated,” said Derrick L. Jackson,
Special Agent in Charge of the Atlanta Region for the Office of
Inspector General of the Department of Health & Human
Services. “HHS/OIG will continue to work closely with our
law enforcement partners to bring these criminals to justice.”

Reginael D. McDaniel, Special Agent in Charge of the
Atlanta Region for Internal Revenue Service Criminal Investigation
said, “Today’s global economy demands a high-level coordinated
approach by multiple agencies and authorities in the investigation
of financial crimes. While schemes often become more
sophisticated over time, fortunately so do our investigative
techniques. IRS Criminal Investigation is proud to have
shared its hallmark expertise in following the money trail in the
scheme alleged in this indictment.”

According to US Attorney Yates, the sordid saga went like this: “In
the
1990s, THORSEN worked as a visiting scientist at the U.S.
Centers for Disease Control and Prevention (CDC), Division of
Birth Defects and Developmental Disabilities, when the CDC was
soliciting grant applications for research related to infant
disabilities. THORSEN successfully promoted the idea of
awarding the grant to Denmark and provided input and guidance for
the research to be conducted. From 2000 to 2009, the CDC
awarded over $11 million to two governmental agencies in Denmark
to study the relationship between autism and exposure to vaccines,
between cerebral palsy and infection during pregnancy, and between
childhood development and fetal alcohol exposure. In 2002,
THORSEN moved to Denmark and became the principal investigator for
the grant, responsible for administering the research money
awarded by the CDC.”

Eleven million dollars constituted I thought, an impressive small
fortune for a few studies, regardless of where they originated.

US Attorney Yates ended by reminding everyone that “the
indictment contains only allegations. A defendant is
presumed innocent of the charges and it will be the government's
burden to prove a defendant's guilt beyond a reasonable doubt at
trial.”

Weeks later, the story with a photograph of the doctor was featured
on the web site of the Office of the Inspector General of HHS.[11]
To this day, the closing sentence still is “Thorsen is currently
in Denmark and is awaiting extradition to the United States.”

The first paragraph of the document also remains as upsetting:

From approximately February 2004 until February 2010,
Poul Thorsen executed a scheme to steal grant money awarded by the
Centers for Disease Control and Prevention (CDC). CDC had awarded
grant money to Denmark for research involving infant disabilities,
autism, genetic disorders, and fetal alcohol syndrome. CDC awarded
the grant to fund studies of the relationship between autism and
the exposure to vaccines, the relationship between cerebral palsy
and infection during pregnancy, and the relationship between
developmental outcomes and fetal alcohol exposure.

I have personally never seen CDC-sponsored Danish studies on infant
disabilities, genetic disorders and fetal alcohol syndrome. If they
exist, they surely did not get the publicity they deserved.

On the other hand, several studies from Denmark on “the relationship
between autism and the exposure to vaccines” that supported the
CDC’s position have certainly been published with great fanfare.

***

Two questions need to be asked:

What was expected from the researchers for 11 million
dollars? Did that in any way constitute a Conflict of Interest?

"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."

-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820

“A sacred cow will not protect the herd.”

-- Sandy Gottstein

"What's the point of vaccination if it doesn't protect you from the unvaccinated?"

-- Sandy Gottstein

"Who gets to decide what the greater good is and how many will be sacrificed to it?"